Neoplastic transformation in pre- and postnatal rat brain by the direct-acting carcinogen N-ethyl-N-nitrosourea (EtNU) provides a model system for the study of chemical carcinogenesis. A single pulse of EtNU specifically leads to a high incidence of neuroectodermal neoplasms, when applied to BD IX-rats at the perinatal age. Fetal rat brain cells transferred to cell culture after exposure to EtNU in vivo, undergo malignant conversion after a sequence of phenotypic alterations. We intend to compare the probability of neoplastic transformation between different tissues and between different cell populations within a given tissue (brain), as a function of their proliferative and differentiative (developmental) state at the time of exposure to EtNU. We are particularly interested in the question whether the cellular capacity to repair carcinogen-modified DNA is connected with the probability of neoplastic transformation. Thus we will compare the elimination rates of the premutational ethylation product 06-ethylguanine from DNA in different rat tissues, neural cell types, and during brain development and differentiation. Characterization of cell populations and stages of development/differentiation with an elevated risk of neoplastic transformation may have considerable relevance in view of cancer prevention.